西地那非治疗肺动脉高压疗效和安全性的初步观察

Sildenafil therapy for pulmonary hypertension： a prospective study

目的探讨西地那非治疗对肺动脉高压患者的临床疗效及耐受性，为西地那非治疗肺动脉高压提供依据。方法连续人选2007年5月至2009年4月阜外心血管病医院收治的肺动脉高压患者56例，其中男1l例，女45例，年龄（31±11）岁。给予西地那非25mg口服，3次／d，记录治疗前和治疗12周后患者心功能和肺动脉高压功能分级、6min步行距离、Borg呼吸困难指数、血流动力学改变及临床症状，同时监测患者血液循环及实验室检测指标及不良反应。结果治疗12周后，患者心功能和肺动脉高压功能分级有明显改善（P〈0．01），其中2例Ⅳ级升高至Ⅲ级；8例Ⅲ级改善为Ⅱ级，2例升高至I级；5例Ⅱ级升高至I级。无纽约心功能分级及世界卫生组织肺动脉高压功能分级恶化病例；6rain步行距离由（352±80）m增加至（396±78）m；差值为（44±70）m（P〈0．01）；肺动脉平均压降低（6±14）mmHg（1mmHg=0．133kPa）、肺血管阻力降低（490±832）Dys·s·cm^-5（均P〈0．01）心输出量增加（1．1±2．0）L／rain，P〈0．01；心指数增加（0．7±1．1）L·min^-1·m^-2（均P〈0。01）。患者无临床恶化情况，耐受性良好，无严重不良事件。结论西地那非治疗可显著改善肺动脉高压患者功能分级，活动耐力及血流动力学。

Objective To explore the safety and efficacy of oral sildenafil therapy for pulmonary arterial hypertension（ PAH）, and to provide evidence for sildenafil treatment for Chinese patients with PAH. Methods In this 12-week, prospective, open-label, uncontrolled study, 56 patients with PAH were given oral sildenafil （25 rag, tid）. The primary end point was change from baseline to 12 weeks in exercise capacity assessed by 6 rain walk （6MW） test. Secondary end points included changes in WHO class and cardiopulmonary hemodynamics. Clinical worsening was defined as death, transplantation, hospitalization for PAH, or initiation of additional therapies for PAH, such as intravenous epoprostenol or oral bosentan. Results After 12 weeks, the compliance was good in 56 patients. Significant improvement was seen in NYHA heart function class and WHO class as compared to baseline（ P 〈 0. 01 ） ： from class IV to class Ⅲ in 2, from class Ⅲ to classⅡ in 8 and to class Ⅰin 2 cases, and from class Ⅱto class Ⅰ in 5 cases. No NYHA heart function class and WHO PAH function class deterioration were observed. Oral sidenafil increased 6MW distance, from （352 ±80） m to （396±78） m, with a change of （44 ±70） m（P 〈0. 01 ）. Significant improvement was seen in hemodynamics （ mean pulmonary artery pressure, P 〈 0. 01 ; cardiac index, P 〈0. 01 ; pulmonary vascular resistance, P 〈0, 01 ） at week 12 as compared with baseline. Mean right atrial pressure decreased （3 ±11 ）mm Hg （1 mm Hg = 0. 133 kPa）, mean pulmonary arterial pressure decreased （6± 14） mm Hg, cardiac output increased （ 1.1 ±2. 0） L/min, cardiac index increased （0. 7±1, 1 ） L . min^- 1 . m^-2and rot＇a] pulmonary resistance decreased （490±831 ） Dys . s . cm^-5 Side effects were mild and consistent with those reported with sildenafil treatment. No statistically significant clinical worsening was observed with sildenafil therapy for PAH patients. Conclusions Sildenafil improves exercise capacity, WHO functional class, and hemodynamics in patients with pulmonary arterial hypertension.